Translational control of stem cell function

Stem cells are characterized by their ability to self-renew and differentiate into many different cell types. Research has focused primarily on how these processes are regulated at a transcriptional level. However, recent studies have indicated that stem cell behaviour is strongly coupled to the regulation of protein synthesis by the ribosome. In this Review, we discuss how different translation mechanisms control the function of adult and embryonic stem cells. Stem cells are characterized by low global translation rates despite high levels of ribosome biogenesis. The maintenance of pluripotency, the commitment to a specific cell fate and the switch to cell differentiation depend on the tight regulation of protein synthesis and ribosome biogenesis. Translation regulatory mechanisms that impact on stem cell function include mTOR signalling, ribosome levels, and mRNA and tRNA features and amounts. Understanding these mechanisms important for stem cell self-renewal and differentiation may also guide our understanding of cancer grade and metastasis. Stem cells are well known to be controlled transcriptionally, but recent studies indicate that pluripotency, cell fate and differentiation depend on the regulation of translation and ribosome biogenesis by mTOR signalling, ribosome levels, and mRNA and tRNA features. Elucidating these stem cell regulatory mechanisms may increase our understanding of tumorigenesis.